Exosomes of bone-marrow stromal cells inhibit cardiomyocyte apoptosis under ischemic and hypoxic conditions via miR-486-5p targeting the PTEN/PI3K/AKT signaling pathway. Issue 177 (May 2019)

• Record Type: Journal Article
• Authors: Sun, Xiang-Hua; Wang, Xu; Zhang, You; Hui, Jie
• Is Part Of: Thrombosis research. Issue 177(2019)
• Page Start: 23
• Page End: 32
• Publication Date: 2019-05
• Subjects: BMSC -- Exosome -- MiR-486-5p -- PTEN/PI3K/AKT -- Apoptosis -- Myocardial ischemia-reperfusion injury; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2019.02.002
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: Background: Myocardial ischemia–reperfusion injury (MIRI) is a major obstacle in the treatment of ischemic heart disease. Recent studies have shown that exosomes—small membrane vesicles secreted by most cell types—could have a protective effect on the ischemic myocardium. In this study we explored the effect of exosomes derived from bone-marrow stromal cells (BMSC-exo) on cardiomyocyte apoptosis and MIRI. Methods: Exosomes were purified from culture media using the ExoQuick kit and observed using transmission electron microscopy. Cell viability was assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell apoptosis was analyzed by flow cytometry using the Annexin-V/PI stain. The expression levels of microRNA (miRNA), messenger RNA (mRNA) and PTEN/PI3K/AKT-pathway-related proteins were detected by qRT-PCR and western blot, respectively. Myocardial ischemia was simulated by incubating H9C2 cells in a hypoxia/reoxygenation (H/R) conditioned rat MIRI model. Results: BMSC-exo induced the proliferation of H9C2 cells and rescued H9C2 cells from apoptosis in the H/R model, indicating that BMSC-exo has a protective effect on cardiomyocyte injury caused by H/R. Using transgenic H9C2 cells, we found that miR-486-5p in BMSC-exo suppressed the H/R-triggered apoptosis of H9C2 cells. In addition, BMSC-exo repressed the expression of PTEN in H9C2 cells via miR-486-5p, and subsequently activated the PI3K/AKT pathway in vitro. Moreover, the myocardial injury caused by ischemia/reperfusion was repaired by BMSC-exo which activates the PI3K/AKT pathway via miR-486-5p in vivo . Conclusion: Our results suggested that exosomes from BMSCs have a protective effect on myocardium ischemic injury. MiR-486-5p carried by BMSC-exo plays a pivotal role in the regulatory process by suppressing PTEN expression, activating the PI3K/AKT signaling pathway, and subsequently inhibiting the apoptosis of injured cardiomyocytes. Highlights: BMSC-exo suppressed cardiomyocyte apoptosis in H/R model; BMSC-exo rescued the myocardial infarction caused by I/R in myocardium; MiR-486-5p in BMSC-exo triggered the protective effect on ischemic myocardium; MiR-486-5p in BMSC-exo protected ischemic myocardium via PTEN/PI3K/AKT pathway.